[Non-enzymatic glycosylation of lipoproteins in the pathogenesis of atherosclerosis in diabetics].
A significant factor associated with hiperglycaemia in diabetes is the resultant post-translational non-enzymatic glycation of plasma and cellular proteins. This process occurs in vivo by direct chemical reaction of glucose with protein alpha and epsilon amino groups. Because of the diverse evidences for direct involvement of non-enzymatic glycation of lipoproteins in the accelerated development of atherosclerosis in diabetic patients, most attention has been focused on the pathological properties of glycated lipoproteins. Glycation of LDL was found significantly increased in diabetic patients compared with normal subjects, even in the presence of good glycemic control. Metabolic abnormalities associated with glycation of LDL include diminished recognition of LDL by the classical LDL-receptor, and enhancement uptake of LDL by a low-affinity, high capacity receptor pathway on macrophages, thus stimulating foam cell formation, an early feature of atherosclerosis. Moreover, glycated LDL are more susceptible to oxidative modification than non-glycated LDL and glycation of LDL may alter their structure sufficiently to render them immunogenic. Being immunogenic, glycated-LDL accumulates in plasma and may enhance cholesterol ester accumulation in macrophages. Non-enzymatic glycation of HDL impairs its recognition by cells and induce a diminished efflux of cholesterol from cell membranes to HDL particles. Furthermore, glycated apolipoprotein A-1 isolated from plasma of diabetic subjects was deficient in activating lecithin: cholesterol acyl transferase, the driving force in reverse cholesterol transport, pathway responsible of the antiatherogenic properties of HDL.
Calvo
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Departamento de Bioquímica Clínica e Inmunología, Facultad de Farmacia, Universidad de Concepción, Chile.
D001161:Arteriosclerosis / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*
D008074:Lipoproteins
Glicación no enzimática de lipoproteínas en la patogenia de la aterosclerosis en el diabético.